Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, Korea.
Anticancer Res. 2010 Jul;30(7):2773-83.
HPV oncoproteins are selectively retained and expressed in HPV infected carcinoma cells. The E7 oncoprotein interacts with the tumour suppressor Rb, and leads to the progression of oncogenesis. In a previous study, E7 biomarkers were identified in E7 Tg mice. In this study, in order to investigate whether a genotoxic carcinogen would modulate carcinogenesis in the E7-Tg mice, an anticancer drug, melphalan, was intraperitoneally injected into E7-Tg mice for eight weeks at two-day intervals and then genes and proteins were analysed using Omics approaches and RT-qPCR. RT-qPCR was performed to confirm whether E7 biomarkers would be modulated by melphalan treatment in E7-Tg mice, revealing that up-regulated E7 markers such as cyclin B1, CD166, and actin alpha1 were down-regulated, whereas expression of down-regulated E7 markers such as vimentin was restored by melphalan treatment. These results suggest that melphalan inhibits carcinogenesis via modulating E7-specific genes and proteins expressed in the lung tissues of E7 Tg mice.
HPV 致癌蛋白在 HPV 感染的癌细胞中被选择性保留和表达。E7 致癌蛋白与肿瘤抑制因子 Rb 相互作用，导致致癌作用的进展。在之前的研究中，已经在 E7 Tg 小鼠中鉴定出了 E7 生物标志物。在这项研究中，为了研究是否一种遗传毒性致癌剂会调节 E7-Tg 小鼠的致癌作用，我们将抗癌药物美法仑以两天一次的间隔通过腹腔注射到 E7-Tg 小鼠中 8 周，然后使用组学方法和 RT-qPCR 分析基因和蛋白质。进行 RT-qPCR 以确认美法仑处理是否会调节 E7-Tg 小鼠中的 E7 生物标志物，结果表明上调的 E7 标志物，如细胞周期蛋白 B1、CD166 和肌动蛋白α1，被下调，而下调的 E7 标志物，如波形蛋白的表达则被美法仑处理所恢复。这些结果表明，美法仑通过调节 E7 Tg 小鼠肺部组织中表达的 E7 特异性基因和蛋白质来抑制致癌作用。
